Genetic Variant FMR1:c.-123_-100dupCGGCGGCGGCGGCGGCGGCGGCGG (chrX-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_002024.6(FMR1):c.-123_-100dupCGGCGGCGGCGGCGGCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 1 hom., 37 hem., cov: 2)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

FMR1
NM_002024.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.618

Variant links:

Genes affected

FMR1 (HGNC:3775): (fragile X messenger ribonucleoprotein 1) The protein encoded by this gene binds RNA and is associated with polysomes. The encoded protein may be involved in mRNA trafficking from the nucleus to the cytoplasm. A trinucleotide repeat (CGG) in the 5' UTR is normally found at 6-53 copies, but an expansion to 55-230 repeats is the cause of fragile X syndrome. Expansion of the trinucleotide repeat may also cause one form of premature ovarian failure (POF1). Multiple alternatively spliced transcript variants that encode different protein isoforms and which are located in different cellular locations have been described for this gene. [provided by RefSeq, May 2010]

FMR1 links:

FMR1-AS1 (HGNC:39081): (FMR1 antisense RNA 1)

FMR1-AS1 links:

ENSG00000274086 (HGNC:):

ENSG00000274086 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant X-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCG is Benign according to our data. Variant chrX-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCG is described in ClinVar as [Benign]. Clinvar id is 763001.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00481 (169/35167) while in subpopulation AMR AF= 0.017 (47/2764). AF 95% confidence interval is 0.0131. There are 1 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 2. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 37 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6 link	c.-123_-100dupCGGCGGCGGCGGCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17	ENST00000370475.9	NP_002015.1	Q06787-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475 link	c.-123_-100dupCGGCGGCGGCGGCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17	1	NM_002024.6	ENSP00000359506.5		Q06787-1

Frequencies

GnomAD3 genomes

AF:

0.00483

AC:

170

AN:

35169

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

AN XY:

5801

show subpopulations

Gnomad AFR

AF:

0.00390

Gnomad AMI

AF:

0.00559

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.00481

Gnomad EAS

AF:

0.00351

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00399

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

6328

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

3418

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00481

AC:

169

AN:

35167

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

AN XY:

5805

show subpopulations

Gnomad4 AFR

AF:

0.00390

Gnomad4 AMR

AF:

0.0170

Gnomad4 ASJ

AF:

0.00481

Gnomad4 EAS

AF:

0.00351

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00120

Gnomad4 NFE

AF:

0.00394

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

X-147912049-CGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over